Dear All,
I'm getting very high entropy values after running the MMPBSA with the
following input.
The vibrational contribution seems very large (-ve) number.
The GBSA based enthalpy looks reasonable since the two proteins are known
to have a weak binding affinity (kb ~ 700 s-1) at 300 K. I was hoping to
combine the Delta-H (from GBSA and PBSA) calculations with Delta-S
calculations to get the total Delta-G and then use Delta-G = -RT * ln(kb)
to see if it agrees with the experimental data.
Can you please help me understand what might be the problem here?
It will also help if you can comment on the correctness of my approach here
and what might be the associated pitfalls. The MMPBSA reference doesn't
seems to address these aspects.
Thus valuable insights and comments are highly appreciated.
Thanks a lot and best regards.
| Run on Mon Apr 19 00:34:17 2021
|
|Input file:
|--------------------------------------------------------------
|Input file for running nmode and GB
|&general
| endframe=2000, verbose=2, interval=5,
| entropy=1,
|/
|&gb
| igb=5,
|
|/
|
|--------------------------------------------------------------
|MMPBSA.py Version=14.0
|Solvated complex topology file: ../1hga-3ner-solv.prmtop
|Complex topology file: 1hga-3ner-complex.prmtop
|Receptor topology file: 1hga-recp1.prmtop
|Ligand topology file: 3ner-lig1.prmtop
|Initial mdcrd(s): ../1hga-3ner-solv-prod300-reimaged.nc
|
|Receptor mask: ":1-143"
|Ligand mask: ":144-235"
|
|Calculations performed using 400 complex frames.
|
|Generalized Born ESURF calculated using 'LCPO' surface areas
|
|All units are reported in kcal/mole.
|All entropy results have units kcal/mol (Temperature is 298.15 K).
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
ENTROPY RESULTS (QUASI-HARMONIC APPROXIMATION) CALCULATED WITH PTRAJ:
Translational Rotational Vibrational Total
Complex: 16.7930 17.5417 888.2178 922.5524
Receptor: 16.3264 16.4191 744.8073 777.5525
Ligand: 15.9981 15.9934 736.5319 768.5234
DELTA S: -15.5315 -14.8708 -593.1214 -623.5235
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
GENERALIZED BORN:
Complex:
Energy Component Average Std. Dev. Std. Err. of
Mean
-------------------------------------------------------------------------------
BOND 844.4563 33.9946
1.6997
ANGLE 2293.4877 33.7218
1.6861
DIHED 1198.4857 18.1241
0.9062
VDWAALS -1734.8917 22.4482
1.1224
EEL -17168.3020 109.5404
5.4770
1-4 VDW 838.9863 12.0959
0.6048
1-4 EEL 12041.8362 58.1348
2.9067
EGB -3376.9606 86.3362
4.3168
ESURF 102.4703 1.7543
0.0877
G gas -1685.9416 106.9086
5.3454
G solv -3274.4903 85.9813
4.2991
TOTAL -4960.4319 48.0756
2.4038
Receptor:
Energy Component Average Std. Dev. Std. Err. of
Mean
-------------------------------------------------------------------------------
BOND 416.0058 16.0560
0.8028
ANGLE 1278.9046 25.4859
1.2743
DIHED 688.8077 14.2048
0.7102
VDWAALS -1105.7934 15.2715
0.7636
EEL -10471.9733 71.2250
3.5612
1-4 VDW 502.2180 9.2879
0.4644
1-4 EEL 7057.2247 31.7299
1.5865
EGB -1272.0252 58.3189
2.9159
ESURF 54.6697 1.3079
0.0654
G gas -1634.6059 73.0947
3.6547
G solv -1217.3554 57.6275
2.8814
TOTAL -2851.9613 35.9199
1.7960
Ligand:
Energy Component Average Std. Dev. Std. Err. of
Mean
-------------------------------------------------------------------------------
BOND 428.4505 29.8335
1.4917
ANGLE 1014.5831 23.9354
1.1968
DIHED 509.6780 12.6930
0.6346
VDWAALS -618.2028 14.6859
0.7343
EEL -6213.0919 78.1662
3.9083
1-4 VDW 336.7683 8.0045
0.4002
1-4 EEL 4984.6115 49.8345
2.4917
EGB -2593.5910 69.7658
3.4883
ESURF 50.4901 1.3869
0.0693
G gas 442.7966 73.9919
3.6996
G solv -2543.1009 69.0004
3.4500
TOTAL -2100.3043 31.4666
1.5733
Differences (Complex - Receptor - Ligand):
Energy Component Average Std. Dev. Std. Err. of
Mean
-------------------------------------------------------------------------------
BOND -0.0000 0.0001
0.0000
ANGLE -0.0000 0.0001
0.0000
DIHED -0.0000 0.0001
0.0000
VDWAALS -10.8955 8.5405
0.4270
EEL -483.2368 81.8501
4.0925
1-4 VDW 0.0000 0.0001
0.0000
1-4 EEL -0.0000 0.0000
0.0000
EGB 488.6556 77.8583
3.8929
ESURF -2.6895 1.3187
0.0659
DELTA G gas -494.1323 85.3064
4.2653
DELTA G solv 485.9660 76.9182
3.8459
DELTA TOTAL -8.1663 10.2147
0.5107
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
Using Quasi-harmonic Entropy Approximation: DELTA G binding = 615.3572
-------------------------------------------------------------------------------
-------------------------------------------------------------------------------
--
Regards,
Dr. Vaibhav A. Dixit,
Visiting Scientist at the Manchester Institute of Biotechnology (MIB), The
University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
AND
Assistant Professor,
Department of Pharmacy,
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Birla Institute of Technology and Sciences Pilani (BITS-Pilani),
VidyaVihar Campus, street number 41, Pilani, Rajasthan 333031.
India.
Phone No. +91 1596 255652, Mob. No. +91-7709129400,
Email: vaibhav.dixit.pilani.bits-pilani.ac.in, vaibhavadixit.gmail.com
http://www.bits-pilani.ac.in/pilani/vaibhavdixit/profile
https://www.linkedin.com/in/vaibhav-dixit-b1a07a39/
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Received on Sun Apr 18 2021 - 10:30:02 PDT
